Phosphatidylserine (PS) is an important marker by which macrophages can recognize and eliminate apoptotic cells (Schlegel, R. A. et al., Cell Death and Differentiation, 2001, 8: 551-563). Normally, phosphatidylserine is present in a cell membrane, but when a cell receives a death signal or red blood cells become old, phosphatidylserine is translocated to the outside of a cell membrane and macrophages recognize the translocated phosphatidylserine via receptors exposed on the cell surface and induce phagocytosis (Fadok, V. A. et al., J Immunol 1992, 148:2207-2216).
Annexin V is a protein which can effectively bind to phosphatidylserine (U.S. Patent Application Publication No. 2013-0302827). When the structure of a cell membrane is destroyed in the early stage of apoptosis, the phosphatidylserine that had been exposed only inside a cell becomes exposed to the outside of the cell membrane. Therefore, annexin V-containing kits developed based on the above are widely used for detecting apoptosis. International Patent Publication No. WO 2009107971A2 discloses a composition for detecting apoptosis containing a polypeptide which is specifically coupled to phosphatidylserine.
Meanwhile, according to the analysis of the health insurance data for the last 10 years released by the Health Insurance Review & Assessment Service of Korea, the total number of diabetic patients in Korea is estimated to be about 7.22 million in 2020, which is about one out of seven people in Korea (i.e., 14.4% of the Korean population) (PARK Youngsu, HANYANG MEDICAL REVIEWS 29 (2), 2009). Accordingly, a huge socioeconomic loss is expected to follow.
These methods for treating diabetes may include a method using oral hypoglycemic agents and insulin and a transplantation method using the pancreas and islets of Langerhans (KIM, Hwajeong et al., J Korean Soc Transplant, December 2009; 23 (3):214-226). Recently, there is a growing interest on the surgeries to recover insulin-secretory function via transplantation of the islets of Langerhans of other people with insulin-secretory function and thus the success rate of the surgery has been improved. The transplantation of the islets of Langerhans is less invasive and more convenient, compared to pancreas transplantation, thus having advantages in that adverse effects due to surgery occur less, hospitalization period becomes shorter, and repeated surgery is possible. Additionally, even when pancreas transplantation is impossible, the transplantation of the islets of Langerhans can be performed by taking them from a donor.
However, when the transplantation is performed according to the Edmonton protocol for islet transplantation widely used at present (Shapiro A M et al., N Engl J Med 2006; 355: 1318-30), the instant blood-mediated inflammatory reaction (IBMIR) may occur due to immune responses in the blood vessel thereby inducing the apoptosis of the islets of Langerhans. When cells from two or more donors are used for transplantation, inflammatory responses may be aggravated due to different HLA antigens and it may cause rejections. Therefore, there is a need to develop a therapeutic method for inhibiting apoptosis during the transplantation of the islets of Langerhans.